The goal of this proposal is to examine the possible protective role of neuropeptides released from cardiac C-fiber afferents during ischemia and reperfusion. The proposed studies will be conducted in isolated, Langendorff perfused rat hearts (global ischemia and reperfusion) and in rat hearts in vivo (regional ischemia and reperfusion). The specific aims are to investigate the role of substance P (SP) and calcitonin gene related peptide (CGRP) in (1) the resistance of the isolated heart to global ischemia and reperfusion, (2) the resistance of the heart in vivo to regional transient ischemia and reperfusion and infarct size, (3) to determine if the effect of the neuropeptides in isolated hearts is mediated by alterations in coronary blood flow, and (4) to determine if the protective effects of bradykinin on cardiac function is mediated by activation of cardiac C-fiber afferents and the release of neuropeptides.